Moteur de recherche interne

Grenoble Institut des Neurosciences

English

Accueil > Nous rejoindre > Offres de stages

Cytoskeleton behavior in the synaptic compartment, implication in Alzheimer’s disease

Objectifs

The objective of the project is to better understand the cross-talk between microtubules and actin filaments in the post-synaptic compartment of cultured neurons in physiological and/or pathological conditions. Different animal models in which microtubules composition is altered (TTL and SVBP mice) and Alzheimer’s disease model (APP/PS1) will be used.

Résumé

During synaptic plasticity, dendritic spines (post-synaptic compartment) exhibit structural changes depending on actin and microtubule cytoskeletons. Microtubules and actin form dynamic networks closely related to each other. Microtubule dynamics is regulated, in part, by post-translational modifications of tubulin, including the tyrosination/detyrosination cycle: tyrosinated tubulin is a marker of dynamic microtubules and detyrosinated tubulin of stable microtubules.
Our group produced transgenic mice lacking the enzymes of the tyrosination/detyrosination cycle: tubulin tyrosine ligase (TTL) and tubulin carboxypeptidase complex VASH-SVBP. We first demonstrated the vital role of tyrosinated tubulin by analyzing the TTL KO mouse. We also described brain abnormalities and cognitive deficiencies in both, TTL and SVBP transgenic mice. Recently, we demonstrated that tubulin tyrosination regulates synaptic function and is disrupted in Alzheimer's disease.
In this project, the student will analyze the behavior and dynamics of actin and microtubules in dendritic spines of cultured neurons from WT and transgenic mice (TTL and SVBP) in which microtubules are modified.
In a next step, depending on the results obtained, he/she will perform the same set of experiments in a pathological context of Alzheimer’s disease, where tyrosination/detyrosination cycle is perturbed.

Méthodes

Techniques used will include cellular biology (primary neuronal cultures, neuron transfection, virus infection, immunofluorescence and confocal microscopy) and biochemistry (brain dissection, subcellular fractionation, western-blot analysis).

Références

Tubulin tyrosination regulates synaptic function and is disrupted in Alzheimer's disease. Peris L, Parato J, Qu X, Soleilhac JM, Lanté F, Kumar A, Pero ME, Martínez-Hernández J, Corrao C, Falivelli G, Payet F, Gory-Fauré S, Bosc C, Blanca Ramírez M, Sproul A, Brocard J, Di Cara B, Delagrange P, Buisson A, Goldberg Y, Moutin MJ, Bartolini F, Andrieux A. Brain. 2022 Feb 11. doi: 10.1093/brain/awab436.

A key function for microtubule-associated-protein 6 in activity-dependent stabilisation of actin filaments in dendritic spines. Peris L, Bisbal M, Martinez-Hernandez J, Saoudi Y, Jonckheere J, Rolland M, Sebastien M, Brocard J, Denarier E, Bosc C, Guerin C, Gory-Fauré S, Deloulme JC, Lanté F, Arnal I, Buisson A, Goldberg Y, Blanchoin L, Delphin C, Andrieux A. Nat Commun. 2018 Sep 17;9(1):3775. doi: 10.1038/s41467-018-05869-z. PMID: 30224655.

Vasohibins/SVBP are tubulin carboxypeptidases (TCP) that regulate neuron differentiation. Aillaud C, Bosc C, Peris L, Bosson A, Heemeryck P, Van Dijk J, Le Friec J, Boulan B, Vossier F, Sanman LE, Syed S, Amara N, Couté Y, Lafanechère L, Denarier E, Delphin C, Pelletier L, Humbert S, Bogyo M, Andrieux A, Rogowski K, Moutin MJ. Science. 2017 Nov 16. pii: eaao4165. doi: 10.1126/science.aao4165.

Domaines d'expertise requis

Primary neuronal cell culture, cell biology, neurobiology, microscopy, biochemistry

Contacts

L. Peris (CR Inserm)
Email : leticia.peris@univ-grenoble-alpes.fr
Phone : 0456520550

Téléchargement(s)

GIN_offre-stage-M2_2022-2023_LPeris_20220707.pdf (PDF, 172390 Ko)

Mise à jour le 8 juillet 2022

Venir au GIN

>> Consulter le plan d'accès

Contacts

Pour les stages (master, licence, 3ème hors sessions décembre et avril), envoyer directement un email au responsable de l'équipe que vous avez identifiée.

Pour une candidature spontanée pour un emploi et uniquement pour cela, envoyez un email à gincomm[at]univ-grenoble-alpes.fr ou utilisez le formulaire de contact.